Postnatal changes in oxygen transport and hemoglobin concentration occur in all species which have been studied. The molecular events which initiate these changes are unknown. We have selected two species, canine and caprine which differ in their apparent mechanisms for modulation of hemoglobin oxygen affinity. The oxygen affinity of whole blood, the concentrations of possible effectors, the activities of the carbonic anhydrase isozymes and the enzyme diphosphoglycerate mutase will be determined during fetal and early postnatal life. We will also monitor any major changes in carbon dioxide transport. Statistical correlations between oxygen affinity and effector concentrations or enzyme activity will be sought. Positive or negative correlations will be tested in vitro by examining the change in oxygen affinity of isolated hemoglobin due to addition of the apparently significant effector. Within this framework we will then confirm the in vivo significance by suitable experimental manipulation. The available possibilities include: a) transfusion of newborn dogs or goats with compatible blood from littermates, b) blood loss anemia, c) exposure to a hypoxic environment, d) modification of red cell diphosphoglycerate concentrations.